Phase I evaluation of CycloSam® (Sm-153-DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma.

153 Sm-DOTMP (CycloSam® ) is a newly-patented radiopharmaceutical for bone tumor treatment. DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate) is a macrocyclic chelating agent with superior binding properties to 153 Sm when compared with EDTMP (Quadramet™, used for palliative treatment of bone cancer). CycloSam® was administered at 1 mCi/kg (37 MBq/kg) in a prospective pilot study to seven dogs with bone cancer resulting in no myelosuppression. Then, 13 dogs were enrolled in a prospective clinical trial study using traditional 3+3 dose escalation and starting at 1.5 mCi/kg. Baseline evaluation included hematologic and biochemical testing, diagnosis confirmation, thoracic and limb radiographs, technetium-99 m-HDP bone scintigraphy, and 18 F-FDG PET scan (SUVmax). Toxicity (primary endpoint) was assessed through weekly blood counts and adverse events. Dogs received 1.5 mCi/kg (n = 4), 1.75 mCi/kg (n = 6), and 2 mCi/kg (n = 3) of 153 Sm-DOTMP. Dose-limiting neutropenia and thrombocytopenia were seen at 2 mCi/kg. No dose-limiting nonhematologic toxicities occurred. Efficacy (secondary endpoint) was assessed by objective lameness measurement (body-mounted inertial sensors), owner quality-of-life (QoL) questionnaire, and repeat PET scan. Objective lameness measurement improved in four dogs (53%-60% decrease) was equivocal in three dogs, and worsened in four dogs (66%-115% increase); two dogs were not evaluable. Repeat 18 F-FDG PET scan results varied and change in lameness did not consistently correlate with SUVmax changes. QoL score worsened (n = 5) or was improved/stable (n = 7). Carboplatin chemotherapy (300 mg/m2 IV every 3 weeks ×4) started 4 weeks after 153 Sm-DOTMP injection. No dog died of chemotherapy-related complications. All dogs completed study monitoring. The recommended dose for CycloSam® in dogs is 1.75 mCi/kg, which resulted in some pain control with minimal toxicity and was safely combined with chemotherapy.

Dosimetric implications of the potential radionuclidic impurities in 153Sm-DOTMP.

Thehuman internal dosimetry of the radionuclidic impurities of samarium-153 in a new bone-seeking radiopharmaceutical, 153Sm-1,4,7,10tetraazacyclododecanetetramethylenephosponic acid (153Sm-DOTMP), has been estimated from preclinical data. The effective dose from the impurities in lower-specific-activity 153Sm is less than 17% of the effective dose from pure Sm-153. It has a background-equivalent radiation time for a dosage of 37 MBq/kg of less than one-half year.

RADAR Guide: Standard Methods for Calculating Radiation Doses for Radiopharmaceuticals, Part 2-Data Analysis and Dosimetry.

This paper presents standardized methods for performing dose calculations for radiopharmaceuticals. Various steps in the process are outlined, with some specific examples given. Special models for calculating time-activity integrals (urinary bladder, intestines) are also reviewed. This article can be used as a template for designing and executing kinetic studies for calculating radiation dose estimates from animal or human data.

RADAR Guide: Standard Methods for Calculating Radiation Doses for Radiopharmaceuticals, Part 1-Collection of Data for Radiopharmaceutical Dosimetry.

This paper presents standardized methods for collecting data to be used in performing dose calculations for radiopharmaceuticals. Various steps in the process are outlined, with some specific examples given. This document can be used as a template for designing and executing kinetic studies for calculating radiation dose estimates, from animal or human data.

Radiation Safety Considerations in the Treatment of Canine Skeletal Conditions Using 153Sm, 90Y, and 117mSn.

The treatment of pets, service animals, and pre-clinical research subjects with radionuclides raises concern for the safety of the people who interact with the animals after their treatment. Three treatments of skeletal conditions in dogs are considered in this study: Sm-1,4,7,10-tetraazacylcododecanetetramethylenephosphonic acid, which is a bone-seeking radiopharmaceutical; unencapsulated Y permanent interstitial implants, which are sometimes called "liquid brachytherapy"; and Sn radiosynoviorthesis, which is also called radiosynovectomy. External exposure rate readings of the Sm and Sn treatments, and Monte Carlo simulations of Sn at a distance of 1 m and of all three in direct contact with tissue were analyzed for doses. Dogs that have received any of these treatments using typically administered activities may be released from radiation safety isolation immediately after treatment from the standpoint of external exposure. People should avoid prolonged close proximity, such as sleeping with a treated dog, for three weeks following an Y interstitial implant or for a month following Sn radiosynoviorthesis. No such avoidance is necessary after treatment with Sm-1,4,7,10-tetraazacylcododecanetetramethylenephosphonic acid.

Prediction of 1p/19q Codeletion in Diffuse Glioma Patients Using Pre-operative Multiparametric Magnetic Resonance Imaging.

This study compared the predictive power and robustness of texture, topological, and convolutional neural network (CNN) based image features for measuring tumors in MRI. These features were used to predict 1p/19q codeletion in the MICCAI BRATS 2017 challenge dataset. Topological data analysis (TDA) based on persistent homology had predictive performance as good as or better than texture-based features and was also less susceptible to image-based perturbations. Features from a pre-trained convolutional neural network had similar predictive performances and robustness as TDA, but also performed better using an alternative classification algorithm, k-top scoring pairs. Feature robustness can be used as a filtering technique without greatly impacting model performance and can also be used to evaluate model stability.

A measurement of the attenuation of radiation from F-18 by a PET/MR scanner.

The attenuation of 511 keV photons by the structure of a PET/MR scanner was measured prior to energizing the magnet. The exposure rate from a source of fluorine-18 was measured in air and, with the source placed at the isocenter of the instrument, at various points outside of the scanner. In an arc from 45 to 135 degrees relative to the long axis of the scanner and at a distance of 1.5 m from the isocenter, the attenuation by the scanner is at least 5.6 half-value layers from the MR component alone and at least 6.6 half-value layers with the PET insert installed. This information could inform better design of the radiation shielding for PET/MR scanners.

HU deviation in lung and bone tissues: Characterization and a corrective strategy.

INTRODUCTION: In the era of precision medicine, quantitative applications of x-ray Computed Tomography (CT) are on the rise. These require accurate measurement of the CT number, also known as the Hounsfield Unit. In this study, we evaluated the effect of patient attenuation-induced beam hardening of the x-ray spectrum on the accuracy of the HU values and a strategy to correct for the resulting deviations in the measured HU values. MATERIALS AND METHODS: A CIRS electron density phantom was scanned on a Siemens Biograph mCT Flow CT scanner and a GE Discovery 710 CT scanner using standard techniques that are employed in the clinic to assess the HU deviation caused by beam hardening in different tissue types. In addition, an anthropomorphic ATOM adult male upper torso phantom was scanned on the GE Discovery 710 scanner. Various amounts of Superflab bolus material were wrapped around the phantoms to simulate different patient sizes. The mean HU values that were measured in the phantoms were evaluated as a function of the water-equivalent area (Aw ), a parameter that is described in the report of AAPM Task Group 220. A strategy by which to correct the HU values was developed and tested. The variation in the HU values in the anthropomorphic ATOM phantom under different simulated body sizes, both before and after correction, were compared, with a focus on the lung and bone tissues. RESULTS: Significant HU deviations that depended on the simulated patient size were observed. A positive correlation between HU and Aw was observed for tissue types that have an HU of less than zero, while a negative correlation was observed for tissue types with HU values that are greater than zero. The magnitude of the difference increases as the underlying attenuation property deviates further away from that of water. In the electron density phantom study, the maximum observed HU differences between the measured and reference values in the cortical bone and lung materials were 426 and 94 HU, respectively. In the anthropomorphic phantom study, the HU difference was as much as -136.7 ± 8.2 HU (or -7.6% ± 0.5% of the attenuation coefficient, AC) in the spine region, and up to 37.6 ± 1.6 HU (or 17.3% ± 0.8% of AC) in the lung region between scenarios that simulated normal and obese patients. Our HU correction method reduced the HU deviations to 8.5 ± 9.1 HU (or 0.5% ± 0.5%) for bone and to -6.4 ± 1.7 HU (or -3.0% ± 0.8%) for lung. The HU differences in the soft tissue materials before and after the correction were insignificant. Visual improvement of the tissue contrast was also achieved in the data of the simulated obese patient. CONCLUSIONS: The effect of a patient's size on the HU values of lung and bone tissues can be significant. The accuracy of those HU values was substantially improved by the correction method that was developed for and employed in this study.

Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT Predicts Bone Marrow Failure After 223Ra Therapy.

PURPOSE: Determine if skeletal tumor burden on 18F-fluoride PET/CT (fluoride PET/CT) predicts the risk of bone marrow failure (BMF) after 223Ra dichloride therapy (223Ra). METHODS: Forty-one metastatic prostate cancer patients (43-89 years old; mean, 71 ± 9 years.) underwent fluoride PET/CT prior to 223Ra. Bone marrow failure was the primary end point and was defined as (1) development of hematologic toxicity (World Health Organization grade 3 or 4) associated with no recovery after 6 weeks or (2) death due to BMF after the last 223Ra dose. Bone marrow failure was correlated to fluoride PET/CT skeletal tumor burden (TLF10 [total lesion on fluoride PET/CT with SUVmax of 10 or greater]), use of chemotherapy, serum hemoglobin concentration, serum ALP, and serum prostate-specific antigen. RESULTS: The number of 223Ra cycles ranged from 2 to 6 (mean, 5). Of the 41 patients, 16 developed BMF (G3 = 12; G4 = 4). A significantly increased risk of developing BMF was observed in patients with TLF10 of 12,000 or greater (hazard ratio [HR], 11.09; P < 0.0001), hemoglobin of less than 10 g/dL (HR, 7.35; P = 0.0002), and AP > 146 UI/L (HR, 4.52; P = 0.0100). Neither concomitant (HR, 0.91; P = 0.88) nor subsequent use of chemotherapy (HR, 0.14; P = 0.84) increased the risk of BMF, nor was prostate-specific antigen greater than 10 µg/L (HR, 0.90; P = 0.86). Moreover, in a multivariable analysis, TLF10 was the only independent predictor of BMF (HR, 6.66; P = 0.0237). CONCLUSIONS: 223Ra was beneficial and reduced the risk of death even in patients with a high skeletal tumor burden. Fluoride PET/CT is able to determine which patients will benefit from 223Ra and which will develop BMF.

Dosimetry of a (90)Y-hydroxide liquid brachytherapy treatment approach to canine osteosarcoma using PET/CT.

A new treatment strategy based on direct injections of (90)Y-hydroxide into the tumor bed in dogs with osteosarcoma was studied. Direct injections of the radiopharmaceutical into the tumor bed were made according to a pretreatment plan established using (18)F-FDG images. Using a special drill, cannulas were inserted going through tissue, tumor and bone. Using these cannulas, direct injections of the radiopharmaceutical were made. The in vivo biodistribution of (90)Y-hydroxide and the anatomical tumor bed were imaged using a time-of-flight (TOF) PET/CT scanner. The material properties of the tissues were estimated from corresponding CT numbers using an electron-density calibration. Radiation absorbed dose estimates were calculated using Monte Carlo methods where the biodistribution of the pharmaceutical from PET images was sampled using a collapsing 3-D rejection technique. Dose distributions in the tumor bed and surrounding tissues were calculated, showing significant heterogeneity with multiple hot spots at injection sites. Dose volume histograms showed that approximately 33.9% of bone and tumor and 70.2% of bone marrow and trabecular bone received an absorbed dose over 200Gy; approximately 3.2% of bone and tumor and 31.0% of bone marrow and trabecular bone received a total dose of over 1000Gy.

A preclinical investigation of the saturation and dosimetry of 153Sm-DOTMP as a bone-seeking radiopharmaceutical.

INTRODUCTION: The therapeutic potential of the bone-seeking radiopharmaceutical 153Sm-labeled 1,4,7,10-tetraazacyclododecanetetramethylenephosphonic acid (153Sm-DOTMP) was assessed by measuring its dosage-dependent skeletal uptake at two chelant-to-metal ratios and its source organ residence times at a chelant-to-metal ratio of 1.5:1. A similar agent, 153Sm-labeled ethylenediaminetetramethylenephosphonic acid (153Sm-EDTMP), has been reported to exhibit dosage-limiting skeletal saturation. METHODS: Sm-DOTMP was prepared with tracer activity of 153Sm and sufficient stable, unenriched Sm to simulate different activities. Cohorts of seven 280-g Sprague-Dawley rats were administered the equivalent of 296, 592, 888, 1184 and 1480 MBq (8, 16, 24, 32 and 40 mCi) at a fixed chelant-to-metal ratio of 1.5:1 and euthanized 3 h after administration. Cohorts of three 128-g Sprague-Dawley rats were administered equivalent dosages of 10.4, 592 and 888 (0.28, 16 and 32 mCi) at a fixed chelant-to-metal ratio of 270:1 and euthanized 2 h after administration. A simulated activity of 1480 MBq (40 mCi) at a chelant-to-metal ratio of 1.5:1 was administered to cohorts of seven rats that were euthanized at 2, 4, 24 or 48 h postadministration. The heart, lungs, liver, spleen, kidneys, small intestine, large intestine, urinary bladder, muscle and a femur were excised, weighed and counted. The data were analyzed to determine skeletal uptake and source organ residence times. RESULTS: No statistically significant skeletal saturation was observed up to human-equivalent dosages of 370 GBq (10 Ci) at a chelant-to-metal ratio of 1.5:1, but the skeletal uptake dropped by 40% over the range of dosages at a chelant-to-metal ratio of 270:1. At a chelant-to-metal ratio of 1.5:1, the preferred ratio, the skeletal uptake fraction in rats was 0.408 (95% confidence interval 0.396-0.419) with an effective half-life of 47.3 h (95% confidence interval 42.3-53.7; the physical half-life of 153Sm is 46.3 h). Extrapolating to an adult human model, 52.9 GBq (1.43 Ci) of 153Sm-DOTMP would deliver 40 Gy to the red marrow. CONCLUSION: 153Sm-DOTMP has dosimetry equivalent to that of 153Sm-EDTMP at low dosages, yet with no skeletal saturation at higher administered activities.

Hybrid Modality Fusion of Planar Scintigrams and CT Topograms to Localize Sentinel Lymph Nodes in Breast Lymphoscintigraphy: Technical Description and Phantom Studies.

Lymphoscintigraphy is a nuclear medicine procedure that is used to detect sentinel lymph nodes (SLNs). This project sought to investigate fusion of planar scintigrams with CT topograms as a means of improving the anatomic reference for the SLN localization. Heretofore, the most common lymphoscintigraphy localization method has been backlighting with a (57)Co sheet source. Currently, the most precise method of localization through hybrid SPECT/CT increases the patient absorbed dose by a factor of 34 to 585 (depending on the specific CT technique factors) over the conventional (57)Co backlighting. The new approach described herein also uses a SPECT/CT scanner, which provides mechanically aligned planar scintigram and CT topogram data sets, but only increases the dose by a factor of two over that from (57)Co backlighting. Planar nuclear medicine image fusion with CT topograms has been proven feasible and offers a clinically suitable compromise between improved anatomic details and minimally increased radiation dose.

Acquisition parameters for oncologic imaging with a new SPECT/multislice CT scanner.

INTRODUCTION: Single photon emission computed tomography/computed tomography (SPECT/CT) delivers in a single imaging modality the functional-metabolic information from the SPECT image, combined with the detailed anatomical information from a diagnostic quality CT scanner. METHOD: In this review, we provide the details for the acquisition, processing, and display of the SPECT, as well as the CT, and the fused SPECT/CT images, with one of the newest devices that combines a dual-headed gamma camera with a multislice CT scanner. Also, we go over the performance characteristics, including the planning and installation requirements for this type of scanners. In addition, we describe what are the current and feasible near-future applications of this new and exciting hybrid imaging modality. DISCUSSION: The ability to combine an optimized state-of-the-art SPECT image, with resolutions down to 5 mm, with a diagnostic quality CT image-using slices as thin as 1.25 mm-provides a diagnostic advantage that potentially can deliver a more convenient and faster diagnosis, with clinical implications in a significant percentage of patients. This imaging technique has been investigated in a wide range of studies for the oncologic patient, including but not limited to bone scintigraphy, (111)In-pentetreotide scintigraphy, lymphoscintigraphy, (67)Ga and labeled leukocyte infection imaging, (131)I-metaiodobenzylguanidine, parathyroid scintigraphy, (131)I diagnostic scintigraphy, and (111)In ProstaScint, and for planning of radionuclide therapy. CONCLUSION: Therefore, this evolving and exciting imaging modality will continue to grow and define its place as an integral part of the evaluation of the cancer patient.

Pilot study of targeted skeletal radiation therapy for bone-only metastatic breast cancer.

PURPOSE: Bone-targeted radiation therapy is an attractive strategy for addressing bone disease with minimal systemic toxicity. This pilot study was designed to determine the safety and efficacy of (166)Holmium (Ho)-DOTMP for irradiating malignant cells and adjacent marrow in women with bone-only metastatic breast cancer. PATIENTS AND METHODS: Subjects included 6 women aged < or = 65 years with breast cancer and bone-only metastases at M. D. Anderson Cancer Center. The activity of (166)Ho-DOTMP was calculated to deliver a therapeutic absorbed dose of 22 Gy (n = 3) or 28 Gy (n = 3) to the marrow. Treatment was followed by autologous stem cell transplantation to circumvent the anticipated myelosuppresion. Median follow-up time was 40 months. RESULTS: All subjects showed prompt hematologic recovery. No patient experienced grade 3/4 acute toxicity aside from myelosuppression. Two patients developed hemorrhagic cystitis 2 years after therapy. One patient developed myelodysplastic syndrome but was found to have had pre-existing trisomy 8. Two patients remained progression free without evidence of disease for more than 6 years. Five women experienced disease relapse (4 at extraosseous sites) and died of progressive disease. Median time to progression was 10.4 months. CONCLUSION: The approach of bone-targeted radiation therapy with (166)Ho-DOTMP had an acceptable toxicity profile, and sustained complete response was obtained in 2 of 6 patients. We are conducting a phase II study to evaluate the efficacy of targeted skeletal radiation therapy for treating bone-only metastases.

A novel method to evaluate gamma camera rotational uniformity and sensitivity variation.

An alternative to the conventional method of performing the AAPM Report 52 rotational uniformity and sensitivity test has been developed. In contrast to the conventional method in which a Co-57 sheet source is fastened to the collimator, this new point-source method acquires the images intrinsically using a Tc-99m point source placed near the isocenter of gantry rotation. As with the conventional method, the point-source method acquires 5 x 10(6) count flood images at four distinct gantry positions to calculate the maximum sensitivity variation (MSV)--a quantitative metric of rotational uniformity and sensitivity variation. The point-source method incorporates corrections for the decay of Tc-99m between acquisitions, the curvature in the image intensity due to variation in photon flux across the detector from a near-field source, and the source-to-detector distance variations between views. The raw point-source images were fitted with an analytic function in order to compute curvature- and distance-corrected images prior to analysis. Five independent MSV measurements were performed using both conventional and point-source methods on a single detector of a dual-headed SPECT system to estimate the precision of each method. The precision of the point-source method was further investigated by performing ten independent measurements of MSV on six different detectors. Correlation between the MSV calculated by the two methods was investigated by performing the test on nine different detectors using both methods. Different levels of sensitivity variations were also simulated on four detectors to generate 40 additional paired points for correlation analysis. The effect of the total image counts on the MSV estimated with the new method was evaluated by acquiring image sequences with 5 x 10(6), 10 x 10(6), and 20 x 10(6) count images. The MSV calculated using the conventional and point-source methods exhibited a high degree of correlation and consistency with equivalence. The precision of the point-source method (0.145%) is lower than the conventional method (0.04%) but sufficient to test MSV. No statistically significant dependence of MSV with the point-source method on the total image counts over a range of (5-20) x 10(6) counts was observed. Curvature correction of the images prior to the generation of difference images renders images more conducive to qualitative inspection for structured, nonrandom patterns. The advantages of the new methodology are that multiple detectors of a gamma camera can be evaluated simultaneously which substantially reduces the time required for MSV testing and the reduced risk of accidental damage to the collimators and patient proximity detection system from having to mount a sheet source on each of the detectors.

Optimal (57)Co flood source activity and acquisition time for lymphoscintigraphy localization images.

UNLABELLED: We evaluated different (57)Co flood source activities and acquisition times to obtain an optimal localization image for breast lymphoscintigraphy that would adequately outline the body and allow detection of nodes seen on the emission scan while minimizing unnecessary radiation exposure to the patient. METHODS: An anthropomorphic thorax breast phantom representing an average-size patient was used to simulate nodes on a breast lymphoscintigraphy scan. The activities in the nodes at the time of acquisition ranged from 37 to 185 kBq (1-5 microCi). Four experiments were performed, consisting of 10-min emission and 3-min localization images. Anterior, posterior, and right and left lateral views of the thorax phantom were acquired, using each of 5 different (57)Co flood sources with activities ranging from 37 to 269 MBq (1.0-7.26 mCi). Ten 1-min localization images for each source were acquired and compared for quality. Three-minute localization images for 2 phantom thicknesses of 10 and 20 cm were acquired to determine the contrast-to-noise ratio for each (57)Co source. The total exposure was measured using an ion chamber survey meter. RESULTS: All sources allowed visualization of the lymphatic nodes in acquisitions as short as 3 min. Images using the 126-MBq (3.41-mCi) source demonstrated an adequate body outline along with visualization of all nodes seen on the emission image. The 37-MBq (1.0-mCi) source did not provide sufficient definition of the body outline, whereas the hotter sources decreased node visualization by increasing the background around the nodes at the same time that they increased the patient exposure. Node activity of 37 kBq (1 microCi) became undetectable on the anterior localization images yet was still visible on the lateral image because of greater attenuation of (57)Co photons. The estimated dose rate from the (57)Co sheet sources was 0.641 microSv/MBq/h. CONCLUSION: Acquiring a 3-min localization scan using a 126-MBq (3.41-mCi) source provided the best combination of clear-body outline and visualization of all nodes seen on the emission image. The estimated dose to the patient from the 126-MBq (3.41-mCi) sheet source was very low (8.7 microSv for unilateral and 13.1 microSv for bilateral). Node detectability decreased in localization images acquired using (57)Co sources of higher activity. This effect would be more pronounced in lymphoscintigrams of thin patients compared with those of patients of average thickness.

166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy.

UNLABELLED: 166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical. METHODS: After two 1.1-GBq administrations of 166Ho-DOTMP, data from whole-body counting using a gamma-camera or uptake probe were assessed for reproducibility of whole-body retention in 12 patients with multiple myeloma. The radiation-absorbed dose to normal organs was estimated using MIRD methodology, applying residence times and S values for 166Ho. Marrow dose was estimated from measured activity retained after 18 h. The activity to deliver a therapeutic dose of 25 Gy to the marrow was determined. Methods based on region-of-interest (ROI) and whole-body clearance were evaluated to estimate kidney activity, because the radiotracer is rapidly excreted in the urine. The dose to the surface of the bladder wall was estimated using a dynamic bladder model. RESULTS: In clinical practice, gamma-camera methods were more reliable than uptake probe-based methods for whole-body counting. The intrapatient variability of dose calculations was less than 10% between the 2 tracer studies. Skeletal uptake of 166Ho-DOTMP varied from 19% to 39% (mean, 28%). The activity of 166Ho prescribed for therapy ranged from 38 to 67 GBq (1,030-1,810 mCi). After high-dose therapy, the estimates of absorbed dose to the kidney varied from 1.6 to 4 Gy using the whole-body clearance-based method and from 8.3 to 17.3 Gy using the ROI-based method. Bladder dose ranged from 10 to 20 Gy, bone surface dose ranged from 39 to 57 Gy, and doses to other organs were less than 2 Gy for all patients. Repetitive administration had no impact on tracer biodistribution, pharmacokinetics, or organ dose. CONCLUSION: Pharmacokinetics analysis validated gamma-camera whole-body counting of 166Ho as an appropriate approach to assess clearance and to estimate radiation-absorbed dose to normal organs except the kidneys. Quantitative gamma-camera imaging is difficult and requires scatter subtraction because of the multiple energy emissions of 166Ho. Kidney dose estimates were approximately 5-fold higher when the ROI-based method was used rather than the clearance-based model, and neither appeared reliable. In future clinical trials with 166Ho-DOTMP, we recommend that dose estimation based on the methods described here be used for all organs except the kidneys. Assumptions for the kidney dose require further evaluation.

AAPM Task Group 108: PET and PET/CT shielding requirements.

The shielding of positron emission tomography (PET) and PET/CT (computed tomography) facilities presents special challenges. The 0.511 MeV annihilation photons associated with positron decay are much higher energy than other diagnostic radiations. As a result, barrier shielding may be required in floors and ceilings as well as adjacent walls. Since the patient becomes the radioactive source after the radiopharmaceutical has been administered, one has to consider the entire time that the subject remains in the clinic. In this report we present methods for estimating the shielding requirements for PET and PET/CT facilities. Information about the physical properties of the most commonly used clinical PET radionuclides is summarized, although the report primarily refers to fluorine-18. Typical PET imaging protocols are reviewed and exposure rates from patients are estimated including self-attenuation by body tissues and physical decay of the radionuclide. Examples of barrier calculations are presented for controlled and noncontrolled areas. Shielding for adjacent rooms with scintillation cameras is also discussed. Tables and graphs of estimated transmission factors for lead, steel, and concrete at 0.511 MeV are also included. Meeting the regulatory limits for uncontrolled areas can be an expensive proposition. Careful planning with the equipment vendor, facility architect, and a qualified medical physicist is necessary to produce a cost effective design while maintaining radiation safety standards.

Observed inter-camera variability of clinically relevant performance characteristics for Siemens Symbia gamma cameras.

We conducted an evaluation of the intercamera (i.e., between cameras) variability in clinically relevant performance characteristics for Symbia gamma cameras (Siemens Medical Solutions, Malvern, PA) based on measurements made using nine separate systems. The significance of the observed intercamera variability was determined by comparing it to the intracamera (i.e., within a single camera) variability. Measurements of performance characteristics were based on the standards of the National Electrical Manufacturers Association and reports 6, 9, 22, and 52 from the American Association of Physicists in Medicine. All measurements were performed using 99mTc (except 57Co used for extrinsic resolution) and low-energy, high-resolution collimation. Of the nine cameras, four have crystals 3/8 in. thick and five have crystals 5/8 in. thick. We evaluated intrinsic energy resolution, intrinsic and extrinsic spatial resolution, intrinsic integral and differential flood uniformity over the useful field-of-view, count rate at 20% count loss, planar sensitivity, single-photon emission computed tomography (SPECT) resolution, and SPECT integral uniformity. The intracamera variability was estimated by repeated measurements of the performance characteristics on a single system. The significance of the observed intercamera variability was evaluated using the two-tailed F distribution. The planar sensitivity of the gamma cameras tested was found be variable at the 99.8% confidence level for both the 3/8-in. and 5/8-in. crystal systems. The integral uniformity and energy resolution were found to be variable only for the 5/8-in. crystal systems at the 98% and 90% confidence level, respectively. All other performance characteristics tested exhibited no significant variability between camera systems. The measured variability reported here could perhaps be used to define nominal performance values of Symbia gamma cameras for planar and SPECT imaging.

Radiation dosimetry of 99mTc-labeled C225 in patients with squamous cell carcinoma of the head and neck.

UNLABELLED: This study assessed the radiation dosimetry of 99mTc-labeled ethylene dicysteine (EC) C225 (EC-C225), a promising radioligand for functional tumor imaging. METHODS: Whole-body scanning was performed on 6 patients with head and neck squamous cell carcinoma up to 24 h after administration of 99mTc-EC-C225. Alternate patients who had been randomized to receive C225 in a phase III trial received 99mTc-EC-C225 before their 20-mg test dose or after their 400 mg/m2 loading dose of unlabeled C225 (patients 1/3/5 and 2/4/6, respectively). Radiation dosimetry was assessed using the MIRD method. RESULTS: The critical organ was the kidney, with an average radiation-absorbed dose for all 6 patients of 0.0274 mGy/MBq. The average total-body absorbed dose was 0.0022 mGy/MBq (0.243 cGy/1,110 MBq). CONCLUSION: The new radiopharmaceutical 99mTc-EC-C225 appears to have reasonable dosimetric properties for a diagnostic nuclear medicine agent. Correlation of the imaging results with clinical findings is the next step.